Cellular signaling in macrophage migration and chemotaxis

Whereas most cells in adult tissues are fixed in place by cell junctions, l eukocytes are motile and able to migrate actively through the walls of bloo d vessels into surrounding tissues. The actin cytoskeleton of these cells p lays a central role in locomotion, phagocytosis, and the regulation of cell shape that are crucial elements of neutrophil and monocyte/macrophage func tion. This review will concentrate on how macrophages in particular control the actin cytoskeleton to generate cell movement and the shape changes req uired for chemotaxis, It has recently become evident that a complex of seve n proteins known as the Arp2/3 complex regulates the assembly of new actin filament networks at the leading front of moving cells. Proteins of the Wis cott-Aldrich. Syndrome Protein (WASP) family bind directly to the Arp2/3 co mplex and stimulate its ability to promote the nucleation of new actin fila ments. Upstream of the WASP family proteins, receptor tyrosine kinases, G-p rotein-coupled receptors, phosphoinositide-3-OH kinase (PI 3-kinase), and t he Rho family of GTPases receive and transduce the signals that lead to act in nucleation through WASP-Arp2/3 action. Although many gaps remain in our understanding, we are now in a position to consider completing signaling pa thways that are initiated front outside the cell to the actin rearrangement s that drive cell motility and chemotaxis.